It is proposed to study mechanisms regulating hypothalamo-pituitary- thyroidal and gonadal function in a variety of physiological conditions with a special emphasis on the late consequences of pathogenic neonatal events. It is planned to test a general theory that the neonatal neuroendocrine control system remains plastic for a brief critical period during which it is subject to organizational influences by normal hormones, foreign substances, and environmental stresses which permanently set its adult regulatory function or "set-point". TSH will be measured in pertinent body fluids and tissues including the pituitary, hypothalamus, and adjacent parts of the brain. In selected instances other pituitary hormones and TRH will be assayed. In conjunction with the usual parameters of thyroidal and gonadal function, TSH synthesis and secretion rates will be measured at rest, after PTU challenge, and after TRH stimulation. It is planned to continue studies of the late consequences of neonatal hypo- and hyperthyroidism, caloric deprivation and treatment with clomiphene, DDT, DNP, morphine, and foreign substances of ecological importance. Hypothalamic implantations of systemically ineffective doses will be used to clarify the site of action of the persistent syndromes consequent to neonatal treatment. Special emphasis will be given to the study of the untreated progeny (F1, F2, F3) of rats with these various neonatal syndromes since these have been shown to manifest predictable endocrine abnormalities.